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1.
Environ Res ; : 118967, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38642643

RESUMO

Sulfadimidine (SM2) is an N-substituted derivative of p-aminobenzenesulfonyl structure. This study aimed to analyze the metabolism of SM2 in carp (Cyprinus carpio). The carps were fed with SM2 at a dose of 200 mg/(kg · bw) and then killed. The blood, muscle, liver, kidney, gill, other guts, and carp aquaculture water samples were collected. The UHPLC-Q-Exactive Plus Orbitrap-MS was adopted for determining the metabolites of SM2 in the aforementioned samples. Twelve metabolites, which were divided into metabolites in vivo and metabolites in vitro, were identified using Compound Discoverer software. The metabolic pathways in vivo of SM2 in carp included acetylation, hydroxylation, glucoside conjugation, glycine conjugation, carboxylation, glucuronide conjugation, reduction, and methylation. The metabolic pathways in vitro included oxidation and acetylation. This study clarified the metabolites and metabolic pathways of SM2 in carp and provided a reference for further pharmacodynamic evaluation and use in aquaculture.

2.
Appl Opt ; 63(7): B59-B69, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437256

RESUMO

Retrieving a phase map from a single closed fringe pattern is a challenging task in optical interferometry. In this paper, a convolutional neural network (CNN), HRUnet, is proposed to demodulate phase from a closed fringe pattern. The HRUnet, derived from the Unet model, adopts a high resolution network (HRnet) module to extract high resolution feature maps of the data and employs residual blocks to erase the gradient vanishing in the network. With the trained network, the unwrapped phase map can be directly obtained by feeding a scaled fringe pattern. The high accuracy of the phase map obtained from HRUnet is demonstrated by demodulation of both simulated data and actual fringe patterns. Compared results between HRUnet and two other CNNS are also provided, and the results proved that the performance of HRUnet in accuracy is superior to the two other counterparts.

3.
J Gen Virol ; 105(2)2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38299799

RESUMO

Zika virus (ZIKV) is a re-emerging RNA virus and causes major public health events due to its link to severe neurological complications in foetuses and neonates. The cGAS-STING signalling pathway regulates innate immunity and plays an important role in the invasion of DNA and RNA viruses. This study reveals a distinct mechanism by which ZIKV restricts the cGAS-STING signalling to repress IFN-ß expression. ZIKV attenuates IFN-ß expression induced by DNA viruses (herpes simplex virus type 1, HSV-1) or two double-stranded DNAs (dsDNA90 and HSV120) in mouse embryonic fibroblasts (MEFs). Notably, ZIKV NS5, the viral RNA-dependent RNA polymerase, was responsible for the repression of IFN-ß. NS5 interacts with STING in the cytoplasm, suppresses IRF3 phosphorylation and nucleus localization and promotes the cleavage of STING K48-linked polyubiquitination. Furthermore, the NS5 methyltransferase (MTase) domain interacts with STING to restrict STING-induced IFN-ß expression. Interestingly, point mutation analyses of conserved methyltransferase active site residue D146 indicate that it is critical for repressing IFN-ß expression induced by STING stimulation in cGAS-STING signalling.


Assuntos
Infecção por Zika virus , Zika virus , Animais , Camundongos , Domínio Catalítico , DNA , Fibroblastos/metabolismo , Imunidade Inata , Interferons , Metiltransferases/metabolismo , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Zika virus/fisiologia
4.
Spine (Phila Pa 1976) ; 49(1): 34-45, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37796171

RESUMO

STUDY DESIGN: Multicenter retrospective observational study. OBJECTIVE: This study aimed to distinguish tuberculous spondylitis (TS) from pyogenic spondylitis (PS) using magnetic resonance imaging (MRI). Further, a novel diagnostic model for differential diagnosis was developed. SUMMARY OF BACKGROUND DATA: TS and PS are the two most common spinal infections. Distinguishing between these types clinically is challenging. Delayed diagnosis can lead to deficits or kyphosis. Currently, there is a lack of radiology-based diagnostic models for TS and PS. METHODS: We obtained radiologic images from MRI imaging of patients with TS and PS and applied the least absolute shrinkage and selection operator regression to select the optimal features for a predictive model. Predictive models were built using multiple logistic regression analysis. Clinical utility was determined using decision curve analysis, and internal validation was performed using bootstrap resampling. RESULTS: A total of 201 patients with TS (n=105) or PS (n=96) were enrolled. We identified significant differences in MRI features between both groups. We found that noncontiguous multivertebral and single-vertebral body involvement were common in TS and PS, respectively. Vertebral bone lesions were more severe in the TS group than in the PS group (Z=-4.553, P <0.001). The patients in the TS group were also more prone to vertebral intraosseous, epidural, and paraspinal abscesses ( P <0.001). A total of 8 predictors were included in the diagnostic model. Analysis of the calibration curve and area under the receiver operating characteristic curve suggested that the model was well-calibrated with high prediction accuracy. CONCLUSIONS: This is the largest study comparing MRI features in TS and PS and the first to develop an MRI-based nomogram, which may help clinicians distinguish between TS and PS.


Assuntos
Espondilite , Tuberculose da Coluna Vertebral , Humanos , Tuberculose da Coluna Vertebral/diagnóstico , Espondilite/diagnóstico por imagem , Coluna Vertebral/patologia , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos
5.
J Cosmet Dermatol ; 23(4): 1217-1223, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38131127

RESUMO

BACKGROUND: Vascular occlusion induced by hyaluronic acid injections is rare, but can lead to severe adverse events, including necrosis, blindness, and cerebral infarction. OBJECTIVE: This study aims to explore methods of reducing the risk of complications such as embolism induced by hyaluronic acid injection, and to study the impact of comprehensive systematic treatment on the prognosis of patients with hyaluronic acid embolism. METHODS: The clinical data of three female patients with vascular occlusion due to hyaluronic acid injection was analyzed. Their median age was 26 years, with symptoms presenting 1-6 h postinjection. Hospital stays averaged 6 days. Two patients had ptosis, diplopia, and severe pain after injection of eyebrows. The other, who had a nose enhancement, experienced facial skin color changes and intense pain. RESULTS: Two patients received comprehensive, systematic treatment based on injectable hyaluronidase. One patient self-discharged after receiving injectable hyaluronidase, antispasmodic, and vasodilator treatment on the night of embolism and returned to the hospital 3 days later with worsening embolism symptoms and received symptomatic treatment again. Two patients who received comprehensive, systematic treatment based on injectable hyaluronidase showed significant improvement, while the patient who did not undergo systematic treatment left scars on the face. CONCLUSION: Vascular occlusion caused by hyaluronic acid facial filling is a severe adverse event, and timely, comprehensive, systematic treatment can effectively improve irreversible damage caused by thrombosis, and even cure it.


Assuntos
Técnicas Cosméticas , Preenchedores Dérmicos , Embolia , Humanos , Feminino , Adulto , Ácido Hialurônico , Hialuronoglucosaminidase , Embolia/etiologia , Embolia/prevenção & controle , Dor/etiologia , Técnicas Cosméticas/efeitos adversos
6.
BMC Infect Dis ; 23(1): 695, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37853312

RESUMO

BACKGROUND AND PURPOSE: Tuberculosis (TB) is the most fatal infectious disease worldwide. Approximately 24.6% of tuberculosis cases are extrapulmonary and predominantly affect the spine. It is difficult to diagnose spinal TB (STB). We aimed to evaluate the diagnostic performance of the Mycobacteria Growth Indicator Tube (MGIT)-960 culture, T-SPOT.TB, Xpert Mycobacterium tuberculosis complex (MTB)/resistance to rifampin (RIF), and Metagenomic Next-Generation Sequencing (mNGS) to detect STB. METHODS: We assessed 126 patients presumed to have STB using these four methods. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using clinical diagnosis as a reference. RESULTS: Of the patients, 41 were diagnosed with STB and 85 with non-STB. In the STB group, the sensitivity, specificity, PPV, and NPV of the MGIT-960 culture were 29.3% (12/41), 100% (85/85), 100% (12/12), and 74.6% (85/114), respectively. The sensitivity, specificity, PPV, and NPV of T-SPOT.TB were 92.7% (38/41), 82.4% (70/85), 58.5% (31/53), and 95.9% (70/73), respectively. The sensitivity, specificity, PPV, and NPV of the Xpert MTB/RIF assay were 53.7% (22/41), 100% (85/85), 100% (22/22), and 81.7% (85/104), respectively. The sensitivity, specificity, PPV, and NPV of mNGS were 39.0% (16/41), 98.8% (84/85), 94.1% (16/17), and 77.1% (84/109), respectively. The sensitivity, specificity, PPV, and NPV of mNGS + Xpert MTB/RIF were 73.2% (30/41), 100% (85/85), 96.8% (30/31), and 72.0% (85/118), respectively. The sensitivity, specificity, PPV, and NPV of the mNGS + T-spot assay were 97.6% (40/41), 100% (85/85), 67.9% (38/56), and 75.9% (85/113), respectively. Moreover, the sensitivity, specificity, PPV, and NPV of T-spot + Xpert MTB/RIF were 95.1% (39/41), 100% (85/85), 72.2% (39/54), and 81.0% (85/105), respectively. CONCLUSIONS: T-SPOT.TB is the most effective method for diagnosing STB; however, Xpert MTB/RIF is more reliable and can detect RIF resistance. Clinicians can use mNGS to identify pathogens in patients with spinal infections; these pathogens appeared to be more meaningful in guiding the clinical management of patients in the non-STB group. The combination of Xpert MTB/RIF and mNGS can improve the early diagnosis rate and drug resistance detection, reduce the diagnostic cycle, and provide early targeted anti-TB treatment for patients with STB.


Assuntos
Mycobacterium tuberculosis , Tuberculose da Coluna Vertebral , Humanos , Mycobacterium tuberculosis/genética , Tuberculose da Coluna Vertebral/diagnóstico , Tuberculose da Coluna Vertebral/tratamento farmacológico , Sensibilidade e Especificidade , Rifampina/farmacologia , Rifampina/uso terapêutico , Valor Preditivo dos Testes , Escarro/microbiologia
7.
Heliyon ; 9(6): e17045, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37484330

RESUMO

The potential to create new ecosystems in rivers is possible through the use of reclaimed water as a replenishment source, although the long-term effects of this method are unknown. In this study, the water quality and aquatic ecological evolution of a newly constructed river replenished by reclaimed water in Beijing (the Jing River) were investigated, and the conventional water quality, phytoplankton indicators, and submerged plant growth conditions from October 2018 to December 2020 were analyzed. Spearman's correlation and redundancy analysis between possible influential environmental factors and algal indicators were conducted. The results show that the major water quality indicators could meet the water quality standards for landscape water. There were seven phyla present, including 322 species of phytoplankton. The phytoplankton density increased, followed by a decreasing trend. Phytoplankton densities at each monitoring site reached 10 × 106 to 25 × 106 cells/L in 2019 before decreasing in 2020, then ranging from 8 × 106 to 20 × 106 cells/L. Phytoplankton growth was influenced by changing water quality and ecosystems. Consequently, the submerged plant coverage rate gradually increased from 2018 (0%) to 2020 (26.27%-37.06%), as did biodiversity. Through the implementation of ecological restoration measures in the Jing River, the reclaimed water environment evolved into a more natural water environment, which could provide some reference for similar areas to use reclaimed water as a water replenishment source.

8.
Sci Total Environ ; 897: 165375, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37422222

RESUMO

Prometryn (PRO) is frequently detected in shellfish of international trade among triazine herbicides because of its wide application in agriculture and aquaculture worldwide. Nevertheless, the variations of PRO remain unclear in aquatic organisms, which affect the accuracy of their food safety risk assessment. In the present study, the tissue-specific accumulation, biotransformation, and potential metabolic pathway of PRO were reported in oyster species Crassostrea gigas for the first time. The experiments were conducted through semi-static seawater exposure with low and high concentrations of PRO (at nominal concentrations of 10 and 100 µg/L) via daily renewal over 22 days, followed by 16 days of depuration in clean seawater. The characterization of prometryn in oysters was then evaluated through the bioaccumulation behavior, elimination pathway and metabolic transformation, comparing with other organisms. The digestive gland and gonad were found to be the main target organs during uptake. In addition, the highest bioconcentration factor of 67.4 ± 4.1 was observed when exposed to low concentration. The level of PRO in oyster tissues rapidly decreased within 1 day during depuration, with an elimination rate of >90 % for the gill. Moreover, four metabolites of PRO were identified in oyster samples of exposed groups, including HP, DDIHP, DIP, and DIHP, in which HP was the major metabolite. Considering the mass percentage of hydroxylated metabolites higher than 90 % in oyster samples, PRO poses a larger threat to aquatic organisms than rat. Finally, the biotransformation pathway of PRO in C. gigas was proposed, the major metabolic process of which was hydroxylation along with N-dealkylation. Meanwhile, the newly discovered biotransformation of PRO in oyster indicates the importance of monitoring environmental levels of PRO in cultured shellfish, to prevent possible ecotoxicological effects as well as to ensure the safety of aquatic products.


Assuntos
Crassostrea , Poluentes Químicos da Água , Animais , Ratos , Crassostrea/metabolismo , Prometrina/metabolismo , Comércio , Poluentes Químicos da Água/análise , Internacionalidade , Água do Mar
9.
Metabolites ; 13(6)2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37367893

RESUMO

Insect metabolites play vital roles in regulating the physiology, behavior, and numerous adaptations of insects, which has contributed to them becoming the largest class of Animalia. However, systematic metabolomics within the insects is still unclear. The present study performed a widely targeted metabolomics analysis based on the HPLC-MS/MS technology to construct a novel integrated metabolic database presenting comprehensive multimetabolite profiles from nine insect species across three metamorphosis types. A total of 1442 metabolites were identified, including amino acids and their metabolites, organic acids and their derivatives, fatty acids (FAs), glycerophospholipids (GPs), nucleotides and their metabolites, and benzene and its substituted derivatives. Among them, 622 metabolites were used to generate a 0 and 1 matrix based on their presence or absence, and these metabolites were enriched in arachidonic acid metabolism, tyrosine metabolism, phenylalanine metabolism, and insect hormone biosynthesis pathways. Our study revealed that there is a high coincidence between the evolutionary relationships of the species and the hierarchical cluster based on the types of metabolites, while the quantities of the metabolites show a high diversity among species. The metabolome of the nine representative insects provides an important platform for implementing the analysis of insect systemic metabolites and biological events at the metabolic level.

10.
J Colloid Interface Sci ; 635: 543-551, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36603537

RESUMO

Graphene derivative materials are widely used as anode component in lithium-ion batteries. However, there is still a lack of reliable and foresighted guides helpful for designing high-performance graphene-based electrode materials. To this end, we strategically chose challenging graphite fluoride as starting material for the derivatization of graphene in order to exclude interference factors. As a result, graphene framework was functionalized with oxygen-containing carboxylate and sulfonate groups and oxygen-free aniline units at a similar functionalization degree. Due to the strong effect of lithiation, out-of-plane p-aminobenzoic acid blocks boosted the lithium-storage capacity of graphene matrix to 636 mAh g-1 at 0.1 A/g, and sulfanilic acid blocks maximized this value to 873 mAh g-1. Sadly, oxygen-free aniline functionalized graphene material only delivered a specific capacity of 88 mAh g-1. Meanwhile, spatial lithiated carboxylate and sulfonate units endowed graphene framework with better rate capability and cycling stability. Such a structure-performance relationship established herein was beneficial for the design and preparation of high-performance graphene derivative electrode materials.

12.
Cell Signal ; 103: 110578, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36581219

RESUMO

Microtubule affinity-regulating kinase 3 (MARK3), a member of the MARK family, regulates several essential pathways, including the cell cycle, ciliated cell differentiation, and osteoclast differentiation. It is important to understand the control of their activities as MARK3 contains an N-terminal serine/threonine kinase domain, ubiquitin-associated domain, and C-terminal kinase-associated domain, which perform multiple regulatory functions. These functions include post-translational modification (e.g., phosphorylation) and interaction with scaffolding and other proteins. Differences in the amino acid sequence and domain position result in different three-dimensional protein structures and affect the function of MARK3, which distinguish it from the other MARK family members. Recent data indicate a potential role of MARK3 in several pathological conditions, including congenital blepharophimosis syndrome, osteoporosis, and tumorigenesis. The present review focuses on the physiological and pathological role of MARK3, its regulation, and recent developments in the small molecule inhibitors of the MARK3 signalling cascade.


Assuntos
Proteínas Serina-Treonina Quinases , Transdução de Sinais , Sequência de Aminoácidos , Microtúbulos/metabolismo , Fosforilação , Proteínas Serina-Treonina Quinases/metabolismo , Humanos
14.
Environ Res ; 218: 115032, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36502909

RESUMO

Reclaimed water is widely concerned as an effective recharge of groundwater and surface water, but trace organic pollutants produced by traditional wastewater treatment plants (WWTPs) would cause environmental pollution (water and soil) during infiltration. Therefore, the effects of reclaimed water containing ofloxacin (OFL) and ciprofloxacin (CIP) in antibiotics polluted natural soil (APNS) were investigated by simulating soil aquifer treatment systems (SATs). The experiment results showed that OFL and CIP in water were adsorbed and microbially degraded mainly at 30 cm, and the concentration of OFL and CIP in soil increased with depth, which were mainly due to the desorption from APNS. Concurrently, the change in replenishment water concentration also significantly affected OFL and CIP in pore water and soil. Although OFL and CIP inhibited the diversity of soil microbial community, they also promoted the growth of some microorganisms. As the dominant bacteria, Proteobacteria and Acidobacteriota can effectively participate in the degradation of OFL and CIP. The degradation effects of soil microorganisms on OFL and CIP were 45.48% and 42.39%, respectively, indicating that soil microorganisms selectively degraded pollutants. This experiment was carried out on APNS, which provided a reference for future studies on the migration of trace organic pollutants under natural conditions.


Assuntos
Poluentes do Solo , Poluentes Químicos da Água , Antibacterianos/análise , Solo , Água , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Ofloxacino/análise , Ciprofloxacina , Poluição da Água , Poluentes do Solo/toxicidade , Poluentes do Solo/análise
15.
Sensors (Basel) ; 22(24)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36559975

RESUMO

As a typical sequence to sequence task, sign language production (SLP) aims to automatically translate spoken language sentences into the corresponding sign language sequences. The existing SLP methods can be classified into two categories: autoregressive and non-autoregressive SLP. The autoregressive methods suffer from high latency and error accumulation caused by the long-term dependence between current output and the previous poses. And non-autoregressive methods suffer from repetition and omission during the parallel decoding process. To remedy these issues in SLP, we propose a novel method named Pyramid Semi-Autoregressive Transformer with Rich Semantics (PSAT-RS) in this paper. In PSAT-RS, we first introduce a pyramid Semi-Autoregressive mechanism with dividing target sequence into groups in a coarse-to-fine manner, which globally keeps the autoregressive property while locally generating target frames. Meanwhile, the relaxed masked attention mechanism is adopted to make the decoder not only capture the pose sequences in the previous groups, but also pay attention to the current group. Finally, considering the importance of spatial-temporal information, we also design a Rich Semantics embedding (RS) module to encode the sequential information both on time dimension and spatial displacement into the same high-dimensional space. This significantly improves the coordination of joints motion, making the generated sign language videos more natural. Results of our experiments conducted on RWTH-PHOENIX-Weather-2014T and CSL datasets show that the proposed PSAT-RS is competitive to the state-of-the-art autoregressive and non-autoregressive SLP models, achieving a better trade-off between speed and accuracy.


Assuntos
Semântica , Língua de Sinais , Humanos , Idioma
16.
BMC Biol ; 20(1): 278, 2022 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-36514097

RESUMO

BACKGROUND: In insects, an interplay between the activities of distinct hormones, such as juvenile hormone (JH) and 20-hydroxyecdysone (20E), regulates the progression through numerous life history hallmarks. As a crucial endocrine factor, JH is mainly synthesized in the corpora allata (CA) to regulate multiple physiological and developmental processes, including molting, metamorphosis, and reproduction. During the last century, significant progress has been achieved in elucidating the JH signal transduction pathway, while less progress has been made in dissecting the regulatory mechanism of JH biosynthesis. Previous work has shown that receptor tyrosine kinase (RTK) signaling regulates hormone biosynthesis in both insects and mammals. Here, we performed a systematic RNA interference (RNAi) screening to identify RTKs involved in regulating JH biosynthesis in the CA of adult Blattella germanica females. RESULTS: We found that the epidermal growth factor receptor (Egfr) is required for promoting JH biosynthesis in the CA of adult females. The Egf ligands Vein and Spitz activate Egfr, followed by Ras/Raf/ERK signaling, and finally activation of the downstream transcription factor Pointed (Pnt). Importantly, Pnt induces the transcriptional expression of two key enzyme-encoding genes in the JH biosynthesis pathway: juvenile hormone acid methyltransferase (JHAMT) and methyl farnesoate epoxidase (CYP15A1). Dual-luciferase reporter assay shows that Pnt is able to activate a promoter region of Jhamt. In addition, electrophoretic mobility shift assay confirms that Pnt directly binds to the - 941~ - 886 nt region of the Jhamt promoter. CONCLUSIONS: This study reveals the detailed molecular mechanism of Egfr signaling in promoting JH biosynthesis in the German cockroach, shedding light on the intricate regulation of JH biosynthesis during insect development.


Assuntos
Blattellidae , Animais , Feminino , Blattellidae/genética , Corpora Allata/metabolismo , Hormônios Juvenis/metabolismo , Metamorfose Biológica , Transdução de Sinais/fisiologia , Mamíferos
17.
Heliyon ; 8(11): e11441, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36406669

RESUMO

Two types of aquatic plants commonly used for the ecological restoration of rivers and lakes, Vallisneria natans (Lour.) Hara and Thalia dealbata Fraser ex Roscoe, were selected and grouped by plant parts (root, stem and foliage), and decomposing release experiments were conducted. The influence of the released substances on the water quality was analyzed, as well as the amount of nutrients released by each part of these two plants. The calculated maximum chemical oxygen demand releases from the foliage of V. natans and the foliage of T. dealbata were approximately 5.4 g/kg and 22.65 g/kg, respectively. Through three-dimensional fluorescence spectrum and parallel factor analyses, the different material compositions of the decomposing liquids from the plants were determined, and the main dissolved organic components of the decomposing liquid of V. natans were amino-acid-like and microbially derived humics, and those T. dealbata were soluble microbial by-product-like substances. The carbon-to-nitrogen ratio and humification index of each experimental group were compared. The experimental results showed that different parts of V. natans and T. dealbata had different rates of nutrient release. The dissolved organic matter in the decomposed solution can be utilized by microorganisms, which have the potential to become additional carbon sources. This study provides a new method for the treatment of aquatic plant litter. Different plant species can be used in combination according to their characteristics to ensure that better results are achieved during water treatment processes that use plant decomposing liquids as additional carbon sources.

18.
Cell Death Dis ; 13(9): 828, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36167821

RESUMO

T-LAK cell-oriented protein kinase (TOPK) is a potential therapeutic target in tumors. However, its role in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) has not been reported. Here, we found that TOPK was highly expressed in ALK-positive NSCLC. Additionally, ALK was identified as another upstream kinase of TOPK by in vitro kinase assay screening. Then, it was proven that ALK phosphorylated TOPK at Y74 in vitro and ex vivo, and the pathways downstream of ALK-TOPK were explored by phosphoproteomic analysis. Subsequently, we demonstrated that inhibiting TOPK enhanced tumor sensitivity to alectinib (an ALK inhibitor). The combination of alectinib and HI-032 (a TOPK inhibitor) suppressed the growth and promoted the apoptosis of ALK-positive NSCLC cells ex vivo and in vivo. Our findings reveal a novel ALK-TOPK signaling pathway in ALK-positive NSCLC. The combination of alectinib and HI-032 might be a promising therapeutic strategy for improving the sensitivity of ALK-positive NSCLC to targeted therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Quinase do Linfoma Anaplásico/genética , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Células Matadoras Ativadas por Linfocina/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Quinases , Transdução de Sinais
19.
Zhen Ci Yan Jiu ; 47(8): 719-23, 2022 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-36036107

RESUMO

OBJECTIVE: To observe the analgesic effect of thumbtack needling therapy and the quality of life in puerpera underwent cesarean section. METHODS: One hundred and thirty-five puerpera underwent cesarean section were randomly divided into a medication group, a sham-thumbtack needling group and a thumbtack needling group, 45 cases in each group. In the medication group, the patient control analgesia (PCA) was given. In the thumbtack needling group, on the base of the regimen as the medication group, acupuncture with thumbtack needles was applied to lower abdominal point (Extra), Zusanli (ST36), Sanyinjiao (SP6), Geshu (BL17), Shenshu (BL23) and Dachangshu (BL25). The needles were retained for 48 hours. During the needle retaining, the sites with the needle embedded were pressed and kneaded for 3 times, 1 min each time, at the interval of 4 to 12 h. In the sham-thumbtack needling group, the sham-thumbtack needles were used; the acupoint selection, operation and treatment course were all the same as the thumbtack needling group. The visual analogue scale (VAS) scores of incision pain and ute-rine contraction pain, the incidence of postoperative adverse reactions, the amount of vaginal bleeding and milk amount in lactation were observed at each time point after the operation separately in each group. RESULTS: Compared with the medication group, the VAS score of incision pain was decreased 8, 12 and 24 h after operation (P<0.05), the VAS score of uterine contraction pain was decreased 8, 12, 24 and 48 h after operation (P<0.05), the lactation score was increased in 24 to 48 h after operation (P<0.05) in both the sham-thumbtack needling group and thumbtack needling group. Compared with the sham-thumbtack needling group, the VAS score of incision pain was decreased 8, 12 and 24 h after operation (P<0.05), the VAS score of uterine contraction pain was decreased 24 and 48 h after operation (P<0.05) in the thumbtack needling group. Compared with those from 2 to 24 h after operation, the vaginal bleeding amount was decreased and the lactation score increased from 24 to 48 h after operation (P<0.05) in all of the three groups. CONCLUSION: The conventional PCA combined with thumbtack needling therapy obtained better analgesic effects on incision dynamic pain and uterine contraction pain in patients after cesarean section as compared with either the simple PCA or the combined treatment with sham-thumbtack needling and medication, and both the thumbtack needling and the sham-thumbtack needling therapy can increase the milk amount of lactation from 24 to 48 h after operation.


Assuntos
Terapia por Acupuntura , Analgesia , Pontos de Acupuntura , Analgésicos , Cesárea , Feminino , Humanos , Dor , Gravidez , Qualidade de Vida , Hemorragia Uterina
20.
Nat Commun ; 13(1): 5077, 2022 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-36038582

RESUMO

Water evaporation is a natural phase change phenomenon occurring any time and everywhere. Enormous efforts have been made to harvest energy from this ubiquitous process by leveraging on the interaction between water and materials with tailored structural, chemical and thermal properties. Here, we develop a multi-layered interfacial evaporation-driven nanogenerator (IENG) that further amplifies the interaction by introducing additional bionic light-trapping structure for efficient light to heat and electric generation on the top and middle of the device. Notable, we also rationally design the bottom layer for sufficient water transport and storage. We demonstrate the IENG performs a spectacular continuous power output as high as 11.8 µW cm-2 under optimal conditions, more than 6.8 times higher than the currently reported average value. We hope this work can provide a new bionic strategy using multiple natural energy sources for effective power generation.


Assuntos
Fontes de Energia Elétrica , Água
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